Inhibition of IL-1β-induced peripheral inflammation by peripheral and central administration of analogs of the neuropeptide α-MSH

Tatsuo Watanabe, Melante E. Hiltz, Anna Catania, James M. Lipton

Research output: Contribution to journalArticle

Abstract

Interleukin-1 (IL-1) is a proinflammatory cytokine. α-MSH(1-13) molecules inhibit inflammation induced by cytokines, other mediators of inflammation, and by peripheral irritants. D-valine substitution in the antiinflammatory/antipyretic message sequence [α-MSH(11-13), Lys-Pro-Val] of α-MSH(1-13) increases the activity of the tripeptide. Our aim was to learn if D-valine substitution also enhances the antiinflammatory activity of the entire α-MSH(1-13) molecule and to determine if an antipyretic D-valine-substituted α-MSH(8-13) molecule is also antiinflammatory. Intraperitoneal injection of a-MSH(1-13) and of (D-Val13)α-MSH(1-13) caused dose-related suppression of ear edema induced in mice by intradermal injection of IL-1β; the two molecules were equipotent. (D-Val13)α-MSH(8-13) likewise inhibited inflammation, but the potency was less than that of the larger molecules. Intracerebroventricular injections of (D-Val13)α-MSH(1-13) and of the unsubstituted molecule were equipotent in reducing inflammation; the (D-Val13)α-MSH(8-13) molecule was less effective. The results support the idea that the α-MSH(1-13) molecule inhibits inflammation and suggest that the L-conformation of α-MSH(1-13) is maximally effective with regard to its antiinflammatory activity. The results with α-MSH(8-13) are consistent with previous findings of lesser antihost response activity of α-MSH fragments that contain the COOH-terminal tripeptide Lys-Pro-Val.

Original languageEnglish
Pages (from-to)311-314
Number of pages4
JournalBrain Research Bulletin
Volume32
Issue number3
DOIs
Publication statusPublished - 1993

Keywords

  • Inflammation
  • Interleukin-1
  • Mice
  • Neutrophils
  • α-MSH

ASJC Scopus subject areas

  • Neuroscience(all)

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